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Biomedical subjects

O Rimoldi

Publications and source records attributed to O Rimoldi.

At least 37 records · Page 2Linked to original sources

Blood flow in myocardial hibernation.

Myocardial hibernation is a state of persistently impaired left ventricular function in patients with coronary artery disease that improves after revascularization. It was thought to be caused by a chronic reduction in resting myocardial blood flow in a segment subtended by a diseased coronary artery. However, recent studies using positron emission tomography have demonstrated that absolute myocardial blood flow (mL/min/g) to hibernating myocardium is within normal limits in most patients. The authors hypothesize that hibernating myocardium may be the result of repetitive myocardial stunning, that is, the reversible contractile dysfunction occurring after an episode of myocardial ischemia despite the return of blood flow to normal. Myocardial stunning has been demonstrated in humans in different clinical settings, and recent studies have provided evidence that repetitive episodes of exercise induced ischemia can lead to cumulative and prolonged left ventricular dysfunction akin to that observed in hibernating myocardium.

Animals↗

Normal values for left ventricular volumes obtained using gated PET.

BACKGROUND: Accurate assessment of left ventricular (LV) volumes provides important insights into myocardial function, being particularly important for diseases of the heart in which there is progressive dilatation of the LV, such as remodeling after myocardial infarction. We have recently validated a method for measuring LV volumes using gated positron emission tomography (PET) with oxygen-15 labeled carbon monoxide (C15O). The present study was performed to establish normal values for LV volumes, in absolute units, using this technique. METHODS: Forty subjects [21 males and 19 females; age 49 +/- 13 years (mean +/- SD), range 24-80; body surface area (BSA) range 1.50-2.18 m2] were studied. End diastolic (EDV) and end systolic volumes (ESV) were calculated by determining the edge of the end diastolic and end systolic blood pool images (obtained using PET with C15O) and summing the volume of the voxels comprising the blood pool. RESULTS: For the overall study population, EDV was 109 +/- 20 ml and ESV 37 +/- 12 ml. When stratified according to gender, these values were: in males, EDV was 117 +/- 18 ml and ESV 42 +/- 18 ml; in females, EDV was 100 +/- 19 ml and ESV 32 +/- 8 ml. The differences between gender groups (EDV: p = 0.0027, ESV: p = 0.0029) were eliminated when volumes were corrected for BSA. CONCLUSIONS: These data will form a database of normal values for comparison with pathological conditions of the heart. PET quantification of LV volumes offers a means of measurement of function using an imaging modality that can also assess regional myocardial perfusion and metabolism during the same study session.

Adult↗

Spectral decomposition in multichannel recordings based on multivariate parametric identification.

A method of spectral decomposition in multichannel recordings is proposed, which represents the results of multivariate (MV) parametric identification in terms of classification and quantification of different oscillating mechanisms. For this purpose, a class of MV dynamic adjustment (MDA) models in which a MV autoregressive (MAR) network of causal interactions is fed by uncorrelated autoregressive (AR) processes is defined. Poles relevant to the MAR network closed-loop interactions (cl-poles) and poles relevant to each AR input are disentangled and accordingly classified. The autospectrum of each channel can be divided into partial spectra each relevant to an input. Each partial spectrum is affected by the cl-poles and by the poles of the corresponding input; consequently, it is decomposed into the relevant components by means of the residual method. Therefore, different oscillating mechanisms, even at similar frequencies, are classified by different poles and quantified by the corresponding components. The structure of MDA models is quite flexible and can be adapted to various sets of available signals and a priori hypotheses about the existing interactions; a graphical layout is proposed that emphasizes the oscillation sources and the corresponding closed-loop interactions. Application examples relevant to cardiovascular variability are briefly illustrated.

Algorithms↗

Model for the assessment of heart period and arterial pressure variability interactions and of respiration influences.

A model which assesses the closed-loop interaction between heart period (HP) and arterial pressure (AP) variabilities and the influence of respiration on both is applied to evaluate the sources of low frequency (LF approximately 0.1 Hz) and high frequency (HF, respiratory rate approximately 0.25 Hz) in conscious dogs (n = 18) and humans (n = 5). A resonance of AP closed-loop regulation is found to amplify LF oscillations. In dogs, the resonance gain increases slightly during baroreceptor unloading (mild hypotension obtained with nitroglycerine (NTG) i.v. infusion, n = 8) and coronary artery occlusion ((CAO), n = 6), and it is abolished by ganglionic transmission blockade ((ARF), Arfonad i.v. infusion, n = 3). In humans, this gain is considerably increased by passive tilt. Different, possibly central, sources of LF oscillations are also evaluated, finding a strong rhythmic modulation of HP during CAO. At HF, a direct respiratory arrhythmia is dominant in dogs at control, while it is considerably reduced during CAO. On the contrary, in humans, a strong influence of respiration on AP is shown which induces a reflex respiratory arrhythmia. An index of the gain of baroreceptive response, alpha cl, was decreased by NTG and CAO, and virtually abolished by chronic arterial baroreceptive denervation (TABD, n = 4) and ARF.

Animals↗

Restraining effects of captopril on sympathetic excitatory responses in dogs: a spectral analysis approach.

This study was planned to clarify the effects of captopril administration on the autonomic control of the circulation in conscious dogs and in dynamic conditions using spectral analysis of R-R interval and systolic arterial pressure (SAP) variabilities. Changes in sympathovagal balance modulating the sinoatrial (SA) node were inferred, respectively, from the low (LFR-R)- and high-frequency (HFR-R) components of R-R variability; LFSAP furnished a marker of sympathetic vasomotor control. Increases in sympathetic activity were induced by three different experimental maneuvers [bilateral carotid occlusion (BCO), coronary artery occlusion (CAO), and dynamic exercise] capable of increasing sympathetic outflow to the SA node and to the vessels. Studies were performed both before and after intravenous captopril administration. During BCO, only LFSAP increased from 4.3 +/- 1.5 to 19.7 +/- 4.1 mmHg2; during CAO, both LFR-R and LFSAP increased, respectively, from 3 +/- 1 to 21 +/- 2 normalized units (nu) and from 4.1 +/- 1.3 to 7.2 +/- 1.5 mmHg2. Dynamic exercise at 2 and 4 km/h progressively raised LFR-R from 8 +/- 2 to 58 +/- 7 and 75 +/- 5 nu, respectively; LFSAP showed a parallel trend increasing from 2.5 +/- 0.7 to 8.04 +/- 1.9 and 12.7 +/- 2.2 mmHg2. In all experimental conditions, captopril significantly (P < 0.05) blunted the increase of LFSAP. A restraining effect on LFR-R was apparent only with CAO. Spectral analysis of cardiovascular variabilities indicates that, in the conscious dog, acute captopril administration has an important inhibitory effect on cardiac sympathetic excitatory mechanisms as well as on sympathetic vasomotor control.

Animals↗

A comparative evaluation of thromboxane receptor blockade, thromboxane synthase inhibition and both in animal models of arterial thrombosis.

The combination of thromboxane (TX) synthase inhibition and prostaglandin (PG) H2/TXA2 receptor antagonism yields enhanced antithrombotic effects as compared with either intervention alone. However, it is not known whether the enhancing effect of TX synthase inhibition is expressed also in the presence of complete blockade of PGH2/TXA2 receptors. Thus we evaluated the antithrombotic effects of increasing doses of the PGH2/TXA2 receptor antagonist L 670596 alone and in combination with a dose of the TX synthase inhibitor FCE 22178 causing > 95% inhibition of platelet TXB2 production. In the dog model of electrically induced coronary thrombosis, occlusion time in control animals (n = 14) averaged 72 +/- 29 min. L 670596 alone dose-dependently antagonized platelet PGH2/TXA2 receptors and prolonged occlusion time. The addition of FCE 22178 displaced the dose-occlusion time relation of L 670596 in a parallel fashion without modifying receptor occupancy. In the rabbit model of copper coil-induced carotid artery thrombosis, occlusion was very rapid (14 +/- 4 min) in control animals (n = 17) and was not modified by either aspirin or FCE 22178. L 670596 caused a dose-related receptor blockade and prolongation of occlusion time. The association with FCE 22178 enhanced significantly the antithrombotic effect of L 670596 at all doses. We conclude that the full therapeutic potential of PGH2/TXA2 receptor antagonism is expressed at > 90% platelet receptor occupancy. The additive effect of TX synthase inhibition suggests that conversion of PGH2 to platelet-inhibitor and vasodilator prostaglandins might be of therapeutic importance, irrespective of the extent of PGH2/TXA2 receptor blockade.

Animals↗

Analysis of neural mechanisms accompanying different intensities of dynamic exercise.

The neural mechanisms accompanying dynamic exercise of different intensities were analyzed in dogs and human subjects by means of autoregressive spectral analysis of heart period and arterial pressure variabilities. In the animal experiments, 8 conscious dogs were examined after implanting a solid state pressure gauge in the left ventricle. Animals were examined at rest and during a treadmill run, at 4 km/h, and 0 degrees incline. The experiments were repeated after chronic alpha 1-adrenoreceptor blockade. During the treadmill run, heart rate and systolic left ventricular pressure increased significantly. Simultaneously, the low frequency (LF, 0.1 Hz) component of pulse interval and of systolic pressure variabilities, ie, markers, respectively, of sympathetic modulation of the SA node and of vasomotor activity, increased significantly (evaluated respectively, in normalized and absolute units). After chronic alpha 1-adrenoreceptor blockade, the increase in LF component of systolic pressure variability was prevented, while that observed in R-R interval variability was maintained. Human studies were carried out with either invasive or noninvasive techniques. In the former approach already described, performed in young hypertensive subjects, arterial pressure was recorded with a high fidelity technique. In the second approach applied to young champion swimmers, only the variability of the R-R interval was examined. In both studies, moderate levels of exercise were accompanied by an increase in the LF component of the spectrum: in the case of arterial pressure variability, this increase was detectable both in absolute and normalized units; vice versa, in the case of R-R variability, since physical exercise is accompanied by a marked abatement of the variance, normalized units had to be used in order to evaluate the shift of the sympathovagal balance in favor of sympathetic overactivity.

Adolescent↗

Assessment of the neural control of the circulation during psychological stress.

In this study, we used spectral analysis of short-term R-R and systolic arterial pressure (SAP) variabilities to estimate the changes in neural control of the circulation produced by psychological stress. The 0.1 Hz low-frequency (LF) component of R-R and SAP variabilities provided a quantitative index of the sympathetic activity controlling heart rate and vasomotion. Conversely the high-frequency (HF) respiratory component of R-R variability provided an index of vagal tone. In conscious dogs we used the seemingly stressful situation of being accompanied for the first time to the experimental laboratory as a stimulus. In human subjects we used mental arithmetic. In both cases LF of R-R and SAP variabilities increased significantly suggesting enhanced sympathetic activity both to the SA node and the vasculature. In man, the index alpha, a measure of the overall gain of baroreceptor mechanisms, was found to be reduced during mental arithmetic. Spectral analysis of cardiovascular variabilities thus suggests that in man and in conscious dogs psychological challenges induce a profound re-arrangement of neural control of the circulation, which appears to be characterised by sympathetic predominance and which can be monitored by this technique.

Adult↗

Reduced cardiovascular sympathetic excitatory responses during iloprost infusion in conscious dogs.

STUDY OBJECTIVE: The aim was to determine the effects of the stable prostacyclin analogue iloprost (ZK 36374) on systemic haemodynamics and on cardiovascular neural control. DESIGN: The buffering effect was examined of intravenous and intracoronary iloprost infusion on the excitatory sympathetic reflexes elicited from the heart by (1) intracoronary injections of bradykinin and (2) transient coronary artery occlusion. SUBJECTS: 22 conscious mongrel dogs of either sex, weight 20-25 kg, were used. MEASUREMENTS AND MAIN RESULTS: ECG, systemic arterial pressure, left atrial pressure, and left ventricular pressure, and contractility (dP/dt) were continuously monitored for the duration of the experiments. Iloprost infusion reduced left ventricular pressure, mean arterial pressure, and dP/dt without causing significant changes in heart rate. Transient non-hypertensive coronary artery occlusion increased heart rate and depressed contractility. During intravenous iloprost infusion, coronary artery occlusion no longer elicited an increase in heart rate, while left ventricular dP/dt was more drastically reduced. This pattern of response was not substantially modified by beta adrenergic blockade, whereas the blockade of muscarinic receptors with atropine was accompanied by hypotension and a greater reduction of dP/dt. The observation of a reduced pressor response to the intracoronary injections of bradykinin during iloprost administration further indicated a restraining effect of iloprost on the sympathetic reflexes elicited from the heart. CONCLUSIONS: The data suggest the hypothesis that the protective effects on the ischaemic myocardium observed with iloprost infusions may arise not only from its vasodilator and antiplatelet properties, but also from its capacity to blunt excitatory sympathetic reflexes.

Animals↗

Sympathetic activation during treadmill exercise in the conscious dog: assessment with spectral analysis of heart period and systolic pressure variabilities.

We studied in seven conscious dogs the dynamic rearrangements in neural control of heart rate and left ventricular pressure during treadmill exercise as assessed by spectral analysis. The presence, at rest, of a major high-frequency component (HF), an indicator of vagal tone, was reverted during exercise to a major low-frequency component (LF), an indicator of sympathetic activation. These changes were blunted by chronic beta and alpha 1 adrenergic receptor blockade.

Animals↗

Analysis of short-term oscillations of R-R and arterial pressure in conscious dogs.

We studied the neural determinants of the second (i.e., high frequency, HF)- and third-order (i.e., low frequency, LF) spontaneous oscillations of heart period (R-R interval) and arterial pressure (AP) in conscious dogs, with the hypothesis that they might furnish quantitative markers of autonomic controlling activities. Spectral analysis of simultaneous R-R and AP variabilities quantified these oscillations that were also evaluated in units normalized by total power to focus on the balance of these two major components. At rest we observed a prevalent HF component (approximately 0.25 Hz) in R-R and AP variabilities that was synchronous with respiration. This HF component of R-R variability disappeared after atropine infusion and can be considered a marker mostly of vagal activity. When baroreceptor unloading, obtained by moderate hypotension, increased sympathetic activity the LF component increased in R-R, systolic, and diastolic AP variabilities. This increase in LF was not present after ganglionic blockade or after chronic arterial baroreceptor denervation. After chronic bilateral stellectomy, hypotension was not accompanied by an increase in LF component of R-R variability, while LF component remained in AP variability. An increase in LF component of R-R and AP variabilities was observed during transient coronary artery occlusion.

Animals↗

Automatic assessment of the interaction between respiration and heart rate variability signal.

The present paper introduces an original method of processing heart rate variability (HRV) and respiration signals as detected respectively through chest electrodes and thoracic belt in dogs under different experimental conditions. Signals are processed as time series synchronous with the occurrence of QRS complexes on ECG signal and auto and cross spectra are accordingly calculated. Two particular bands appear mainly of interest on the spectrum of HRV signal: one in correspondence with the respiration rate and another one at a lower frequency value. Values of power at these frequency bands together with coherence and phase between HRV signal and respiration complete the parameters which try to quantify a few aspects of the complex dynamic relationships between the original signals. In particular, controlled respiration in dogs was studied through the connection with an automatic ventilator, as well as the effects of drugs which interact with the neural regulatory systems (i.e. sympathetic and parasympathetic nervous system). Gain and phase relationships between heart rate variability and respiration, obtained with spectral analysis, could be used to provide a better understanding of the neural control mechanisms linking heart rate and respiration in various experimental conditions. The method described in this study is to be used both in physiological and clinical research.

Animals↗

Effects of verapamil, nifedipine, and dilazep on left ventricular relaxation in the conscious dog.

The cardiac systolic and diastolic effects of the two major calcium blockers, verapamil and nifedipine, were studied and compared with those produced by dilazep, a relatively new vasodilator with calcium blocking properties, in conscious instrumented dogs to avoid the complications of anaesthesia and recent surgery. Mean arterial pressure was reduced by nifedipine and dilazep but not by verapamil, whereas peak left ventricular pressure was reduced only by dilazep and verapamil. Consistent tachycardia occurred, the rate being highest with nifedipine and lowest with dilazep. Left ventricular dP/dt was unaffected by dilazep, reduced by verapamil, and increased by nifedipine; this increase was no longer observed after beta adrenergic blockade. Ventricular relaxation was assessed by calculating the time relaxation constant, tau. Verapamil increased tau significantly only after beta adrenergic blockade, whereas nifedipine and dilazep reduced it both before and after beta adrenergic blockade. These data suggest that reflex beta adrenergic mechanisms may modulate the effects of calcium blockade on both systolic and diastolic performance.

Animals↗